1. Field of the Invention
The present invention relates to novel 2-aryl-1,2-benzisothiazolinone-1,1-dioxide compounds and methods of selectively inhibiting proteases especially elastase, and of treating emphysema and rheumatoid arthritis and other inflammatory diseases using the novel compounds.
2. Description of the Prior Art
Various 2-aryl-1,2-benzisothiazolinone-1,1-dioxide compounds have been prepared in the past. Louis L. Bambas, Chemistry of Heterocyclic Compounds, Vol. 4, pp. 330-339, Interscience Publishers (1952), discloses 2-phenyl-, 2-(4-nitrophenyl)-, 2-phenylsulfonyl-, 2-(2-chlorocyclohexyl)-, and 2-(2-,3-, and 4-tolyl)-1,2-benzisothiazolinone-1,1-dioxide. However, none of these 2-aryl-1,2-benzisothiazolinone-1,1-dioxide compounds is the same as the compounds of the present invention, and they do not have and would not suggest the activity of the compounds of the present invention in methods of selectively inhibiting proteases, especially elastase, and of treating emphysema, rheumatoid arthritis, and other inflammatory diseases.
R. Fischer and H. Hurni, in "On Benzisothiazolones: A Series with a Wide Range of Bacteriostatic and Fungistatic Activity", Arzneimittel Forschung, 14 (12) 1301 (1964), disclose a large number of benzisothiazolones. However, none of these benzisothiazolones are 1,1-dioxide compounds, and they are thus not the same as the compounds of the present invention. Moreover, they do not have and would not suggest the activity of the compounds of the present invention in methods of selectively inhibiting proteases, especially elastase, and of treating emphysema, rheumatoid arthritis, and other inflammatory diseases.
German Offenlegungsschrift No. 26 36 599 discloses certain acyl saccharins and methods of inhibiting elastase and treating emphysema with such compounds. However, those acyl saccharin compounds are not the same as the compounds of the present invention, and it is unexpected that the compounds of the present invention are more stable compounds and provide a greater degree of specificity of protease inhibition activity, which is therapeutically valuable.